EP3659631A1 - Pansement comprenant de l'acide hyaluronique-calcium et de la polylysine et procédé de fabrication s'y rapportant - Google Patents

Pansement comprenant de l'acide hyaluronique-calcium et de la polylysine et procédé de fabrication s'y rapportant Download PDF

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Publication number
EP3659631A1
EP3659631A1 EP18839106.4A EP18839106A EP3659631A1 EP 3659631 A1 EP3659631 A1 EP 3659631A1 EP 18839106 A EP18839106 A EP 18839106A EP 3659631 A1 EP3659631 A1 EP 3659631A1
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Prior art keywords
hyaluronic acid
calcium
wound dressing
polylysine
pll
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EP18839106.4A
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German (de)
English (en)
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EP3659631A4 (fr
EP3659631B1 (fr
Inventor
Hyang Mae UM
Ja Young Seol
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Youreh Co Ltd
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Youreh Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/425—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0052—Mixtures of macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/785—Polymers containing nitrogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/225—Mixtures of macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/28—Polysaccharides or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/44—Medicaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/64—Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/0066—Medicaments; Biocides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/0085—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/009—Materials resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23—Carbohydrates
    • A61L2300/236—Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/424—Anti-adhesion agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/04—Materials for stopping bleeding
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/16—Cooling
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2105/00—Condition, form or state of moulded material or of the material to be shaped
    • B29K2105/04—Condition, form or state of moulded material or of the material to be shaped cellular or porous
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/753—Medical equipment; Accessories therefor

Definitions

  • the present invention relates to a wound dressing comprising hyaluronic acid-calcium and polylysine, and a preparation method thereof.
  • Previously-developed hemostatic products include sponge-type Tachocomb® Topical Thrombin which contains in vivo hemostatic coagulation factors and thereby can promote blood coagulation, and Surgicel®, Avitene®, ChitoClot® and the like, which absorb blood and thereby exhibit a blood-coagulation effect. Since Tachocomb® Topical Thrombin contains fibrinogen, thrombin, collagen and the like which are extracted from blood of cows or humans, it may cause a risk of infection and a hypersensitivity reaction during treatment. In addition, Surgicel®, Avitene® and ChitoClot® are disadvantageous in that blood coagulation performance and adhesiveness to an injured area are insufficient, and that the regeneration at the bleeding area is insignificant due to its low biocompatibility,. Accordingly, various wound dressings have been developed for treating injured wounds having an excellent hemostatic performance.
  • wound dressings used for wound healing of skin provide a moist environment suitable for healing, and should meet the requirements such as infection prevention, heat-retaining effect, prevention of adhesion between would surfaces, easiness of use, economic efficiency, absorptive property, moisture permeability, and the like.
  • wound dressings used for deep body cavity are applied to a wound area inside the living body, in addition to the common wound dressing requirements as described above, they must be hydrated in vivo to protect the wound during the wound healing period, but they must be naturally absorbed and removed after the healing is completed, so as not to affect normal tissues, and they also must have anti-adhesion functions.
  • Adhesion refers to a phenomenon that when the healing reaction continues for a long period of time during the healing process of injuries caused by inflammation, wounds, friction, surgery, etc., fibrous tissue is produced excessively, or blood is flowed out and coagulated, and thereby, the surrounding organs or tissues, which should be separated from each other, are adhered to each other. Such phenomenon may occur after all kinds of surgery. In general, it has been known that the incidence of long-term adhesion after surgery reaches 55% to 93%.
  • film-type anti-adhesives have an excellent adhesion inhibitory effect, but they have a limitation in that it is difficult to apply for a microscopic surgery using a laparoscope, the applicability of which has recently been expanded. Meanwhile, solution-type anti-adhesives are disadvantageous in that they are not easily adhered to the wounds due to exudates such as blood or the like which is appeared after surgery, and they may be removed together with the exudates or rapidly absorbed in the peritoneum. As a result, their role as a barrier for preventing adhesion does not last sufficiently.
  • the molecular weight of the hyaluronic acid is in a range suitable for being decomposed and removed in the body after it is applied to the deep body cavity and wound healing is completed, preferably in a range of 2 ⁇ 10 6 to 3 ⁇ 10 6 Da, which has been known as having proper in vivo half-life for acting as a physical barrier.
  • Calcium salts that can be used for such substitution may be, for example, an inorganic acid salt or an organic acid salt such as calcium chloride, calcium acetate and the like, but are not limited thereto, and any calcium salts of inorganic acid or organic acid known in the art may be used without any limitation.
  • Step (1) the pH values of the aqueous solutions of hyaluronic acid-calcium salt and polylysine solution are respectively adjusted to 8.4 or higher, and then the aqueous solutions of hyaluronic acid-calcium salt and polylysine are mixed together to prepare a mixed solution.
  • HA and PLL of which pH values are respectively adjusted to pH 8.4, are mixed in the amounts shown in Table 1 to prepare mixed solutions with 10 ml each in total volume, and the solutions were stabilized at 0 to 4°C for 6 to 10 hours, frozen at -10 to -20°C for 10 to 12 hours, and then freeze-dried to prepare HA-PLL foam-type wound dressings (hereinafter, also referred to as 'HA-PLL pad' or 'HA-Ca-PLL pad'), and the formation of foam was observed.
  • 'HA-PLL pad' or 'HA-Ca-PLL pad' HA-PLL foam-type wound dressings
  • the mixed solution having a composition of Example 2 was poured into a 10 cm ⁇ 10 cm mold, and allowed to stand in a 40°C incubator for 12 to 16 hours to prepare a film-type wound dressing.
  • FIG. 2 shows that compared with the pad prepared only with 0.5% HA-Ca (i.e., HA-Ca content was 0.5% (w/v) based on the total volume of the preparation solution), the pores of the pad prepared by additionally mixing with 0.5% PLL (i.e., HA-Ca content was 0.5% (w/v) and PLL content was 0.5% (w/v) based on the total volume of the preparation solution) were denser.
  • HA-Ca i.e., HA-Ca content was 0.5% (w/v) based on the total volume of the preparation solution
  • the ratio of calcium substitution for the pads prepared from Examples 2 and 5, and Comparative Examples 1 and 2 were determined by Ca quantification using EDTA according to the following procedure: About 0.1 g of the pad was taken, and dissolved in 25 mL of distilled water and 3 mL of buffer solution (pH 10.0), and then 6 drops of EBT indicator was added. The resulting solution was titrated with an EDTA reagent until red color changed to blue.
  • the EDTA reagent was prepared by dissolving 0.3 g Na 2 H 2 EDTA ⁇ 2H 2 O (which was dried at 80°C for 1 hour and stored in a desiccator) in 250 mL of distilled water.
  • FIG. 5 is a photographic image showing results of blood elution test for pure blood, pads containing 0.5% hyaluronic acid-calcium and polylysine-containing depending on their PLL contents, and Comparative Examples 1, and 3 to 5.
  • FIGs. 6 and 7 are graphs showing the absorbance (O.D.) calculation results according to the PLL content when the HA content is 0.5% and 1.0%, respectively.
  • the 1% HA-Ca and 0.5% HA-Ca pads showed a better hemostatic performance when PLL was mixed, and the hemostatic performance was the best when the PLL content was 0.5%. When the PLL content was 0.5% or more, the hemostatic performance was rather decreased.
  • the 1% HA and 0.5% HA pads showed no difference in hemostatic performance, but the 0.5% HA pad showed a faster blood absorption rate. In view of cost, it was concluded that the 0.5% HA-containing pad would be better.
  • Algi Derm and RegenPack both had excellent hemostatic performance, but the pads prepared in the Examples of the present invention showed a higher hemostatic performance than the commercially available products. RegenPack had disadvantage of having a low blood absorption rate.
  • foam-type pads respectively containing hyaluronic acid-calcium salt (HA-Ca), hyaluronic acid-sodium salt (HA-Na), hyaluronic acid-calcium and polylysine (HA-Ca-PLL), and hyaluronic acid-sodium and polylysine (HA-Na-PLL) were prepared in the same manner as in Examples, and the absorbances of the blood eluates were determined in the manner as described in Experimental Example 2. The results are shown in FIG. 9 .
  • the hyaluronic acid pad (HA-Na) without calcium substitution had no hemostatic performance, and the hyaluronic acid pad (HA-Ca) substituted only with calcium showed hemostatic performance. Therefore, it can be implied that calcium improved hemostatic performance.
  • the pad (HA-Na-PLL) prepared by mixing only PLL without calcium substitution showed some hemostatic performance.
  • the pad prepared from calcium-substituted hyaluronic acid also showed hemostatic performance, but the hemostatic performance was found to be higher when the pad was further mixed with PLL (HA-Ca-PLL).
  • a rat cecal/abdominal wall abrasion model was used to evaluate the anti-adhesion performance of the wound dressings prepared in the above Examples.
  • Five 7-week-old male Sprague-Dawley rats (SLC, Japan) were used per each group as experimental animals.
  • the experimental animal was anesthetized by peritoneal administration of Ketamin.HCL (0.1 ml/100 g), its abdominal hair was removed, it was sterilized with 70% ethanol, and then a 4 to 5 cm incision was made on the midline at its abdomen.
  • the wound pad prepared only with hyaluronic acid without polylysine in Comparative Example 1 even showed a higher anti-adhesion effect, compared with Comparative Examples 4 and 5 which are commercially available wound pads.
  • the tissue adhesion was significantly reduced in the experimental groups treated with the wound pads of Examples 1 to 3 of the present invention which were prepared with mixing polylysine at a concentration of 0.25%, 0.5% and 0.75%, respectively, compared with the control group.
  • a pad was prepared by crosslinking HA and PLL with a crosslinking agent.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Hematology (AREA)
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  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Materials For Medical Uses (AREA)
EP18839106.4A 2017-07-26 2018-07-25 Pansement comprenant de l'acide hyaluronique-calcium et de la polylysine et procédé de fabrication s'y rapportant Active EP3659631B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR20170094693 2017-07-26
PCT/KR2018/008397 WO2019022493A1 (fr) 2017-07-26 2018-07-25 Pansement comprenant de l'acide hyaluronique-calcium et de la polylysine et procédé de fabrication s'y rapportant

Publications (3)

Publication Number Publication Date
EP3659631A1 true EP3659631A1 (fr) 2020-06-03
EP3659631A4 EP3659631A4 (fr) 2021-04-14
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EP3659631A4 (fr) 2021-04-14
KR20230125136A (ko) 2023-08-29
US20210228768A1 (en) 2021-07-29
US20240066179A1 (en) 2024-02-29
JP6868314B2 (ja) 2021-05-12
KR20190012120A (ko) 2019-02-08
WO2019022493A1 (fr) 2019-01-31
EP3659631B1 (fr) 2023-08-30
CN110997019A (zh) 2020-04-10
JP2020527987A (ja) 2020-09-17
KR102667393B1 (ko) 2024-05-20

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